tbuckley/cabot-search huggingface dataset:
Toxicities associated with sacituzumab govitecan: Data from clinical trials and real-word pharmacovigilance database.
Authors: Xiangping Mei, Qiaoyun Tan, Jing Yao
Journal: Journal of Clinical Oncology (2023)

e24093 Background: This study aimed to analyze the adverse effect of sacituzumab govitecan (SG) with multiple source data, to provide reference for clinical medication safety management. Methods: Clinical trials of SG with available safety data were searched and included in the pooled analysis (up to January 5th, 2023). The adverse drug reaction (ADR) signals of SG were collected from the FDA Adverse Event Reporting System (FAERS) database up to January 1st, 2023. The ADR signals were presented and sorted by incidence frequency and reporting odds ratio (ROR) strength, respectively. We also searched and summarized drug interactions with SG in DDInter database. Results: A total of 6 clinical trials enrolled 1737 patients were included in pooled analysis, the most common adverse events of ≥3 grade were neutropenia (51.55%), leukopenia (14.50%), anemia (10.69%), diarrhea (7.30%), fatigue and asthenia (4.23%). In pharmacovigilance study, 1024 AE reports were extracted, the most common toxicities of SG are hematologic and gastrointestinal. AEs not included in the instructions also showed high signals, such as meningitis, colitis and lymphedema. A total of 40 drugs identified can induce drug-drug interaction when concomitant administration with SG. Conclusions: This study provides a comprehensive profile of SG based on clinical trial, FRAES and DDInter database, attention should be paid not only to the common ADRs, but also to the ADRs not reported in the drug instructions and potential drugs that induce drug-drug interactions. [Table: see text]
Long-term efficacy of BRAFi/MEKi rechallenge in metastatic melanoma: Report of 9 years of clinical practice.
Authors: Anna Malgorzata Czarnecka, Bozena Cybulska-Stopa, Iga Plachta, Pawel Rogala, Łukasz Galus, Karolina Piejko, Robert Dziura, Wieslaw Bal, Tomasz Kubiatowski, Pawel Teterycz, Magdalena Wisniewska, Marcin Zietek, Piotr Brandys, Natasza Kempa-Kamińska, Aneta Borkowska, Rafał Suwiński, Grażyna Kamińska-Winciorek, Jacek Mackiewicz, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2023)

e21550 Background: First line BRAFi/MEKi therapy in metastatic melanoma eventually result in drug resistance and disease progression. Because drug resistance develops at least partially by epigenetic mechanisms, it may potentially be reversed after BRAFi/MEKi discontinuation. Therefore we aim to explore the clinical efficacy of BRAFi/MEKi rechallenge in 3 line treatment. Moreover the reports on the efficacy of BRAFi/MEKi after immunotherapy were contradictory, so we enrolled patients treated sequentially to explore this clinical scenario. Methods: In country-wide multicenter retrospective analysis 86 patients with metastatic BRAF-mutated melanoma were enrolled since 1/Jan/2014. Patients were treated with 1st line BRAFi/MEKi, 2nd line immunotherapy (anti-PD-1 or anti-CTLA-4) and were rechallenged with BRAFi/MEKi. Survival analyses were performed using the Kaplan-Meier method, log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2022. Results: Median age at BRAFi/MEKi rechallenge was 50 (range: 20-81 y/o). Median overall survival (OS) from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 34 and 9 months, respectively; whereas median progression-free survival (PFS) was 10.5 and 4.4 months respectively. At the time of analysis 88% progressed on third line therapy and 78% patients died. Six-month, one-year, and two-year OS rates were: 99%, 93% and 70% on first line treatment; and 65%, 40% and 2% on BRAFi/MEKi rechallenge. Objective response rate and disease control rate on first line BRAFi/MEKi and rechallenge were 57% and 28%; and 91% and 64%, respectively. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. The most common treatment sequence was dabrafenib/trametinib – immunotherapy – encorafenib/binimetinib. Conclusions: Rechallenge with BRAFi/MEKi after second line immunotherapy results in a clinically significant benefit in majority of eligible patients. Third line treatment should be considered for fit patients. [Table: see text]
Real-world use of tisagenlecleucel in children and young adults with relapsed or refractory B-cell lymphomas.
Authors: Jonathan Bender, Sudarshawn Damodharan, Amy Moskop, Keri Toner, Anant Vatsayan, Christian Capitini, Christina Baggott, Deborah E. Schiff, Emmanuel Katsanis, Sunil S. Raikar, Julie-An M. Talano, Liora M. Schultz, Lauren Pommert
Journal: Journal of Clinical Oncology (2023)

10031 Background: Survival for pediatric B-cell lymphomas (BCL) exceeds 90% with modern regimens, however outcomes remain poor for patients with relapsed or refractory (R/R) disease. Tisagenlecleucel is a CD19-directed CAR T-cell therapy (CART) that is FDA approved for adults with R/R BCL. No data exists for use of tisagenlecleucel in R/R pediatric BCL. Methods: We surveyed 48 sites in the Pediatric Real-World CAR Consortium to retrospectively describe use and outcomes of tisagenlecleucel for pediatric patients with R/R BCL. This cohort included 10 patients from 7 centers aged ≤25 years who were infused between 2019-2022 and were ≥3 months from CART. We aimed to describe response rates, as determined by each institution based on positron emission tomography, bone marrow evaluation, and/or cerebrospinal fluid (CSF) studies, along with toxicity and outcomes in this population. Results: Ten patients received CART with a median age at infusion of 19 (range, 7-24) years. Five patients had B-lymphoblastic lymphoma (B-LLy), 2 had primary mediastinal BCL, and 1 each had Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and post-transplant lymphoproliferative disorder related DLBCL. Five patients had primary refractory disease, and 5 were in ≥2 nd relapse. Three had received prior hematopoietic stem cell transplant (HSCT). Two had CSF involvement, and 1 had central nervous system parenchymal disease at time of infusion. CART was well tolerated with 1 patient experiencing grade 3 cytokine release syndrome and 2 patients experiencing neurotoxicity (grade 2 n = 1, grade 3 n = 1), both of whom had CSF involvement at time of CART infusion. Best overall response was complete response (CR) for 6, partial response (PR) for 2, and refractory disease for 2. Two patients, both with B-LLy, underwent allogeneic HSCT while in CART-mediated CR with B-cell aplasia. Both patients with PR (1 DLBCL, 1 Burkitt) subsequently relapsed with CD19-negative disease; the patient with DLBCL subsequently achieved CR with salvage immuno-chemotherapy and HSCT. All 6 CR patients remain in remission at a median time to follow-up of 31 (range, 14-47) months. Conclusions: This multicenter case series of CD19-directed CART for R/R pediatric BCL suggests that tisagenlecleucel may be safe and active in this population with all CR patients currently in sustained remission. Larger studies are needed to understand how best to incorporate CART into treatment for R/R pediatric BCL. [Table: see text]
Comorbidities in patients with sarcoma: Insights from the National In-Patient Database from 2006 to 2014.
Authors: Maria Cristina Cuartas Mesa, Karol Quelal Analuisa, Rafaella Litvin, Vaishali Deenadayalan, Ayobami Gbenga Olafimihan, Muhammad Bilal Ibrahim, Gianfranco Bittar, Enrique Francisco Martinez Trevino, Alejandro Nieto
Journal: Journal of Clinical Oncology (2023)

e23534 Background: Sarcoma represents a rare solid malignancy in adults. Given the likelihood of metastatic disease, the prognosis is usually poor. Comorbidities are independent determinants of prognosis, and cardiovascular and respiratory diseases are the most common. We aimed to study the prevalence, trends, and outcomes of CVD and pulmonary circulation disorders in patients admitted with sarcoma over eight years. Methods: We present a retrospective analysis of hospital admissions for soft tissue malignancies between 2006 and 2014 from the NIS database using its respective ICD-9-CM code. We obtained the prevalence of cardiovascular diseases (HF, CAD, HTN) and pulmonary circulatory disorders (PE, PHTN). We assessed yearly trends with the Cochran-Armitage trend test. Using multivariate binomial logistic regression (adjusting for sex, race, age, and Elixhauser comorbidities) we calculated adjusted odds ratios (aOR) to identify the association of these comorbidities with in-hospital mortality. Results: Between 2006-2014 there were 352320 admissions with a primary diagnosis of soft tissue malignancies. Of them, 55.8% were males, 60% were white, and 57.5% were 50 years old and older. In 39% of the population, CVD was present: HTN 35.5%, CAD 8.5%, HF 4.5%. The rate of pulmonary circulatory disorders was 2.5%: PE 1.7%, and pulmonary hypertension 0.9%. In-hospital mortality accounted for 3.7% of admissions. The CVD yearly prevalence increased from 34.6% in 2006 to 41.7% in 2014 (p &lt; 0.001). Pulmonary circulatory disorders rose from 1.7% in 2006 to 3.3% in 2014 (p &lt; 0.001). Pulmonary circulatory diseases were associated with high in-hospital mortality aOR 3.02 (CI 95% 2.44-3.73, p = 0.00). Cardiovascular disease was not statistically significantly associated with an increased rate of in-hospital mortality aOR 1.04 (CI 95% 0.93-1.15, p = 0.53). Conclusions: In sarcoma patients, it is essential to quantify their comorbidities as these often influence their chosen therapy. Cardiovascular disease affected one-third of the patients. However, despite the low prevalence of pulmonary circulatory disorders, they were associated with high in-hospital mortality. Further studies are needed to understand the causality and underlying physiopathology.
Efficacy and safety of first-line (1L) nivolumab plus relatlimab (NIVO + RELA) versus NIVO plus ipilimumab (NIVO + IPI) in advanced melanoma: An indirect treatment comparison (ITC) using patient-level data (PLD).
Authors: Dirk Schadendorf, Hussein A. Tawbi, Evan J. Lipson, F. Stephen Hodi, Paolo Antonio Ascierto, James Larkin, Christopher D. Lao, Jean-Jacques Grob, Flavia Ejzykowicz, Andriy Moshyk, Viviana Garcia Horton, Jenny Zhou, Yiqiao Xin, Jennell Palaia, Laura McDonald, Sarah Keidel, Anthony Salvatore, Leon A. Sakkal, Georgina V. Long
Journal: Journal of Clinical Oncology (2023)

9552 Background: NIVO + RELA and NIVO + IPI are approved as dual checkpoint inhibitor, 1L treatment options for patients (pts) with advanced melanoma based on results from the RELATIVITY-047 (NIVO + RELA vs NIVO; enrollment, 2018–2020) and CheckMate 067 (NIVO + IPI or NIVO vs IPI; enrollment, 2013–2014) trials, respectively. However, there is no head-to-head trial comparing the combinations; therefore, this ITC was conducted using PLD. Methods: To adjust for cross-trial imbalances in baseline characteristics, inverse probability of treatment weighting (IPTW) was used. Database locks were selected to best align follow-ups in RELATIVITY-047 (min., 21 mo; median, 25 mo) and CheckMate 067 (min., 28 mo; median, 29 mo). Efficacy and safety outcomes were selected based on data availability, including progression-free survival (PFS) per investigator, confirmed objective response rates (ORRs) per investigator, overall survival (OS), treatment-related adverse events (TRAEs), and TRAEs leading to discontinuation (DC). Efficacy was also evaluated in key subgroups. PFS and OS were compared for NIVO + RELA vs NIVO + IPI using Kaplan–Meier curves and hazard ratios (HRs); ORRs were compared using odds ratio (OR). As an internal validation of the ITC and matched assessments, the weighted NIVO cohorts from both trials were compared. Results: After IPTW, key baseline characteristics were balanced for NIVO + RELA (n = 340) and NIVO + IPI (n = 298). PFS, confirmed ORR, and OS after IPTW were similar between the treatments (table). Efficacy outcomes appeared to be similar between the treatments across subgroups, although trends favoring NIVO + IPI were observed for certain subgroups, such as pts with BRAF mutant disease or lactate dehydrogenase more than twice the upper limit of normal. Grade 3/4 TRAEs occurred in 23% and 61% of pts receiving NIVO + RELA and NIVO + IPI, respectively; any-grade TRAEs leading to DC occurred in 17% and 40% of pts. Efficacy outcomes were similar between the NIVO cohorts (table). Conclusions: In the absence of head-to-head trials, this ITC suggests that 1L treatment with NIVO + RELA may have comparable efficacy to, and better tolerability than, NIVO + IPI in pts with advanced melanoma. Similar outcomes between the NIVO cohorts support the ITC methodology. Results should be interpreted with caution given differences in study design and changes in treatment landscape over time. [Table: see text]
Evaluating the efficacy and safety of pembrolizumab monotherapy or in combination with standard chemotherapy in the first-line treatment of locally recurrent head and neck squamous cell carcinoma in different TP53 and PI3K statuses.
Authors: Shurong Zhang, Boyao Zhang, Xinyu Li, Shoutao Dang, Jingyang Zhao
Journal: Journal of Clinical Oncology (2023)

e18014 Background: Pembrolizumab (pembro)-based therapy is currently widely used in recurrent/metastatic head and neck squamous-cell carcinoma (R/M HNSCC). The study will explore the association between different TP53 and PI3K statuses and survival in locally recurrent HNSCC. Methods: This is a prospective, single-center study analyzing patients with locally recurrent HNSCC and prior platinum-based chemotherapy for at least 6 months without progression. Patients received pembro monotherapy (200mg) or pembro plus standard chemotherapy (PF, TP, P, G, GP; paclitaxel 175mg/m 2 , cisplatin 100 mg/m 2 , 5-fluorouracil 1000 mg/m 2 per day for 4 consecutive days, Gemcitabine 1000mg/m 2 day 1 and day 8) every 21-day for 6 cycles and followed by pembro maintenance therapy until progression or unacceptable toxicity or 35 cycles, whichever occurred first. Patient’s response to the therapy was evaluated using RECIST 1.1. Primary endpoint was PFS ITT ,PFS TP53mut ,PFS TP53wt , PFS PI3Kmut/amp and PFS PI3Kwt . Secondary endpoint was ORR, DCR and OS of ITT patients and combination group. Results: From January 8, 2020 until September 20 2022, 20 patients were enrolled. Median age was 56 (range 47-73). Baseline HPV positive (1,5%), HPV negative (12,60%) and HPV unknow (7,35%). TP53mut (9,45%) and TP53wt (7,35%), TP53 unknow (4,20%). PI3Kmut/amp (2,10%) and PI3Kwt (11,55%), PI3K unknow (7,35%). CPS≥20 (3,15%), CPS 1-19 (9,45%), CPS unknow (8,40%). Primary region showed that 1 patients (5%) in the oral cavity, 2 (10%) in the oropharynx, 7 patients (35%) in the larynx, 4 (20%) in the hypopharynx, 2 (10%) in the sins, 1 (5%) in the epithelial-myoepithelial and 3 (15%) in the unknown primary site. There were 16 patients (80%) with only local recurrent disease, 4 (20%) with local disease combined with distant diseases at enrollment. Median follow-up was 2 years. Adverse reactions are overall controllable (Table), but who one died with grade 4 cardiotoxicity The mPFS ITT was 4.9 months, PFS mono was 4 months and PFS combination was 4.93 months (p=0.89). The mPFS ITT+TP53mut was 5.1 months, mPFS ITT+TP53wt was 4.6 months (p=0.63). mPFS ITT+PI3Kmut/amp was 7.2 months and mPFS ITT+PI3Kwt was 4.6 months. The ORR ITT was 73.7% (14/19) and no complete response was achieved. The ORR combination was 66.7% (10/15). The DCR ITT and DCR combination were all 100% . (Not included 1 died). The median OS was not reached. Conclusions: This study proves that pembro alone and combined with standard chemotherapy has good efficacy and safety in locally recurrent HNSCC, and the statuses of TP53 and PI3K may be an important factor for the prognosis of immunotherapy. Acknowledgement: Thanks MSD China Medical Affair oncology team for giving scientific support. Clinical trial information: ChiCTR2100046731 . [Table: see text]
Chronic leukemias and COVID-19: An analysis of mortality and morbidity outcomes in the United States.
Authors: Ziad Abuhelwa, Ahmad Y Abuhelwa, Mohammad Safi, Jehad Zeidalkilani, Andrew Abrahamian, Sadik Khuder, Roland T. Skeel
Journal: Journal of Clinical Oncology (2023)

e18783 Background: COVID-19 pandemic has resulted in a global health crisis with widespread mortality and morbidity. Patients with chronic leukemias (CL) are at an increased risk for severe outcomes due to their compromised immune system. Despite the potential impact of COVID-19 on this population, there is a scarcity of information on the outcomes for CL patients. Our study aims to evaluate the mortality and morbidity of COVID-19 in CL patients in the United States. Methods: In this retrospective cohort study, we employed the National Inpatient Sample database of 2020, the largest inpatient database in the United States, to include adult patients (age ≥ 18 years) with chronic leukemias (CL) who were hospitalized for COVID-19, as identified by ICD-10-CM codes. The primary outcome was all-cause in-hospital mortality, while the secondary outcomes were acute respiratory failure (ARF) and the requirement for mechanical ventilation (MV). To identify the predictors of mortality, we conducted multivariable logistic regression analyses, with a p-value of less than 0.05 being considered statistically significant. Additionally, we conducted sensitivity analyses based on the type of CL (chronic lymphocytic leukemia (CLL) or chronic myeloid leukemia (CML)) and the remission status (in remission, not achieved remission, and relapse). The statistical analysis was performed using STATA software. Results: Among 91,375 patients with CL, 5.2% were hospitalized for COVID-19, with 87% of these patients having CLL. The majority of the CL patients (88.6%) had not achieved remission. The mean age of the patients was 72.7 years, with 62.4% being male and 78.9% being white. The mortality rate among CL-COVID-19 patients was 17%, with no significant difference in mortality rates between patients with and without CL (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.81-1.14, p-value 0.65). About 61.5% of CL-COVID-19 patients had ARF and only 10.5% required MV. Patients with CL showed a 16% increase in the odds of ARF (OR 1.16, 95% CI 1.01-1.32, p-value 0.03) while no significant difference was found in the odds of MV. Sensitivity analysis showed no significant differences in mortality, ARF, or MV rates between CLL and CML groups. Another analysis by remission status revealed that patients who had not achieved remission had higher odds of ARF (OR 1.64, 95% CI 1.09-2.46, p-value 0.018) compared to those in remission or relapse. Conversely, patients in remission had a significantly lower likelihood of ARF (OR 0.63, 95% CI 0.41-0.97, p-value 0.036). No significant differences in mortality and MV odds were found according to remission status. Conclusions: Our findings emphasize the importance of vigilant monitoring and management of CL patients during the COVID-19 pandemic, particularly for those who have not achieved remission, to reduce their risk of severe respiratory outcomes.
Assessing gender disparities in young patients with lung cancer among a diverse urban population.
Authors: Kyle Edwards, Aysswarya Manoharan, Blanca Noriega Esquives, Leana Ramos, Nora El-Abbar, Nitin Parikh, Samuel A. Kareff, Gilberto Lopes, Estelamari Rodriguez, Coral Olazagasti
Journal: Journal of Clinical Oncology (2023)

e18874 Background: Lung cancer is the leading cause of cancer mortality in the United States and has a higher mortality rate in men. While most patients are typically elderly adults, research shows that rates of lung cancer among younger patients have been increasing. Furthermore, younger patients with lung cancer have unique clinicopathologic characteristics. Methods: A total of 139 lung cancer patients (59 Male and 80 Female) who were under the age of 45 and treated at the University of Miami between 2012-2021were included. Demographics and clinicopathologic characteristics were analyzed. Results: The median age at diagnosis for female and male patients was 39.6yrs vs 38.4yrs. (Table 1) Among females, 28% were White non- Hispanic (NH), 47% were White Hispanic, 8% were Black NH, 2% were Black Hispanic and 11% were of other race. Among males, 38% were White non- Hispanic (NH), 44% were White Hispanic, 8% were Black NH, 5% were Black Hispanic and 3% were of other race. While 67% of male patients smoked tobacco, only 43% of female patients endorsed a history of smoking tobacco (p = 0.005). Male patients underwent surgery after an average of 22 days from diagnosis compared to 17 days for female patients. Moreover, 40% of females had surgical resection compared to 29% of males. The average number of days between a positive biopsy and initiation of chemotherapy for male vs female patients was 39 days vs 36 days, respectively. Female patients had higher trends of adenocarcinoma (68%) and actionable mutations (62%) than their male counterparts (44% and 42%). Lastly, they had lower trends of metastatic disease at diagnosis (58%) than male subjects (62%). Conclusions: Lung cancer trends in older adults appear to remain consistent in younger patients. Young male patients smoke cigarettes significantly more than young female patients. While no other statistically significant differences were found, our study noted a few trends. Overall, females presented with localized disease at a higher rate and had a higher percentage of actionable mutations. Male patients appeared to be more likely to present with systemic disease, which reduced the opportunity for surgical resection. Further prospective studies will be of paramount importance to explore these trends in large cohorts. [Table: see text]